ClinVar Miner

Submissions for variant NM_000314.6(PTEN):c.-1059C>G

gnomAD frequency: 0.00405  dbSNP: rs144620057
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000710302 SCV000840479 benign PTEN hamartoma tumor syndrome 2016-09-14 reviewed by expert panel curation PTEN c.-1059C>G (NC_000010.10:g.89623167C>G) meets criteria to be classified as benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (Mester et al. 2018; manuscript in preparation). Please see a summary of the rules and criteria codes in the 'PTEN ACMG Specifications Summary' document (assertion method column). BA1: Allele frequency of 0.0138 (1.38%, 120/8698 alleles) in the African subpopulation of the gnomAD cohort. (PMID 27535533)
GeneDx RCV000588148 SCV000149463 benign not provided 2017-01-04 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25669429, 21633361, 24154570)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588148 SCV000696523 benign not provided 2017-02-01 criteria provided, single submitter clinical testing Variant summary: The PTEN variant c.-1059C>G (also known as c.-1060C>G) involves the alteration of a non-conserved nucleotide located in the 5' UTR. The variant of interest was observed in 1000 Gs with an allele frequency of 19/5008 (1/270), predominantly in the African cohort, 18/1322 (1/73), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic PTEN variant of 1/158730 for Cowden syndrome and 1/64102 for HBOC. Therefore, suggesting this variant is likely a benign polymorphism found predominantly in population(s) of African origin. Furthermore, another large, broad control population, gnomAD, which is currently only in early beta mode, cites the variant with an allele frequency of 119/8482 (2 homozygotes) in Africans, further supporting the variant being a benign polymorphism. However, of note, the variant has been depicted in ClinVar as c.-1059C>G (the variant's legacy name), with a classification of "likely benign." The variant has been reported in publications and has indicated that it could affect expression. However, due to the high frequency in controls and the supporting classification by a clinical diagnostic laboratory as "likely benign," the variant of interest has been classified as Benign.

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